BACKGROUND: Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD. METHODS: Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon γ [IFN-γ], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, RORγt; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability. RESULTS: Patients with CD showed increased IFN-γ or T-bet cells and decreased IL-13 or Gata3 cells compared with UC. A discriminant equation composed of 4 markers (IFN-γ, T-bet, IL-13, and Gata3) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3 cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-γ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively. CONCLUSIONS: The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.
BACKGROUND: Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD. METHODS: Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon γ [IFN-γ], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, RORγt; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability. RESULTS:Patients with CD showed increased IFN-γ or T-bet cells and decreased IL-13 or Gata3 cells compared with UC. A discriminant equation composed of 4 markers (IFN-γ, T-bet, IL-13, and Gata3) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3 cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-γ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively. CONCLUSIONS: The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.
Authors: Michael J Rosen; Rebekah Karns; Jefferson E Vallance; Ramona Bezold; Amanda Waddell; Margaret H Collins; Yael Haberman; Phillip Minar; Robert N Baldassano; Jeffrey S Hyams; Susan S Baker; Richard Kellermayer; Joshua D Noe; Anne M Griffiths; Joel R Rosh; Wallace V Crandall; Melvin B Heyman; David R Mack; Michael D Kappelman; James Markowitz; Dedrick E Moulton; Neal S Leleiko; Thomas D Walters; Subra Kugathasan; Keith T Wilson; Simon P Hogan; Lee A Denson Journal: Gastroenterology Date: 2017-01-26 Impact factor: 22.682
Authors: Monica Viladomiu; Charles Kivolowitz; Ahmed Abdulhamid; Belgin Dogan; Daniel Victorio; Jim G Castellanos; Viola Woo; Fei Teng; Nhan L Tran; Andrew Sczesnak; Christina Chai; Myunghoo Kim; Gretchen E Diehl; Nadim J Ajami; Joseph F Petrosino; Xi K Zhou; Sergio Schwartzman; Lisa A Mandl; Meira Abramowitz; Vinita Jacob; Brian Bosworth; Adam Steinlauf; Ellen J Scherl; Hsin-Jung Joyce Wu; Kenneth W Simpson; Randy S Longman Journal: Sci Transl Med Date: 2017-02-08 Impact factor: 17.956